Publications by authors named "Biman Saikia"

75 Publications

Prevalance of Anti-HLA antibodies in parous female blood donors: A pilot study from tertiary care hospital of North India.

Asian J Transfus Sci 2021 Jan-Jun;15(1):16-20. Epub 2021 Jun 12.

Department of Immunopathology, PGIMER, Chandigarh, India.

Background: Various studies have implicated that plasma causing transfusion-related acute lung injury is from alloimmunized females. The frequency of sensitization to human leukocyte antigen (HLA) was found to correlate with their parity score. No literature on the prevalence of anti-HLA antibodies in Indian blood donors is available to date. Hence, this pilot study was done to know the frequency of HLA alloimmunization in Indian blood donors.

Materials And Methods: A total of 192 consenting voluntary blood donors from blood donation camps were enrolled in the study. Test group: Parous female donors ( = 96) and control group: Nulliparous female donors ( = 48) and male donors ( = 48). HLA alloimmunization was tested on the Luminex platform by screening assay to detect IgG antibodies to HLA Class I and II molecules of human origin. A mean fluoresence index of more than 2000 was considered as a positive reaction, considering the high sensitivity of Luminex assay.

Results: Sixty-three out of 192 donors (32.8%) tested positive for anti-HLA antibodies, out of which 23 donors were in the control group (23.9%), and 40 donors were in the test group (41.7%); = 0.002. On gender-based comparison, 9 out of 48 male donors (18.7%), as compared to 54 out of 144 female donors (37.5%), tested positive for HLA antibodies ( = 0.02). Based on an increase in parity score, the frequency of HLA alloimmunization was found to be significantly correlated ( = 0.002). A decrease in the trend of HLA alloimmunization was observed as the duration from the last pregnancy increased. A higher frequency of HLA alloimmunization was observed in female donors with a history of transfusion and bad obstetric history.

Conclusion: The present study substantiates that plasma from parous female donors has a higher chance of containing anti-HLA antibodies as compared to nulliparous female and male donors.
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http://dx.doi.org/10.4103/ajts.AJTS_30_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294446PMC
June 2021

Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.

J Exp Med 2021 Aug 17;218(8). Epub 2021 Jun 17.

Garvan Institute of Medical Research, Darlinghurst, Australia.

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be dominant negative (DN), and it has been recently suggested that eight out-of-frame variants operate by haploinsufficiency. We experimentally tested these 143 variants, 7 novel out-of-frame variants found in HIES patients, and other STAT3 variants from the general population. Strikingly, all 15 out-of-frame variants were DN via their encoded (1) truncated proteins, (2) neoproteins generated from a translation reinitiation codon, and (3) isoforms from alternative transcripts or a combination thereof. Moreover, 128 of the 135 in-frame variants (95%) were also DN. The patients carrying the seven non-DN STAT3 in-frame variants have not been studied for other genetic etiologies. Finally, none of the variants from the general population tested, including an out-of-frame variant, were DN. Overall, our findings show that heterozygous STAT3 variants, whether in or out of frame, underlie AD-HIES through negative dominance rather than haploinsufficiency.
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http://dx.doi.org/10.1084/jem.20202592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217968PMC
August 2021

Immunological response and clinical profile in patients with recurrent dermatophytosis.

Mycoses 2021 May 19. Epub 2021 May 19.

Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host.

Objectives: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis.

Methods: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed.

Results: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17 cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4 cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis.

Conclusions: Reduced IFN-γ , Th1, IL-17 and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.
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http://dx.doi.org/10.1111/myc.13322DOI Listing
May 2021

Clinical Profile of Hyper-IgE Syndrome in India.

Front Immunol 2021 26;12:626593. Epub 2021 Feb 26.

Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility to skin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES. A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis. Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%). infections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12. The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant. diseases were more frequent, compared to western literature.
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http://dx.doi.org/10.3389/fimmu.2021.626593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952512PMC
February 2021

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India.

Front Immunol 2021 25;12:625320. Epub 2021 Feb 25.

Department of Pediatric Hematology and Oncology, Kanchi Kamakoti Child Trust Hospital, Chennai, India.

Background: Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India.

Objective: To describe infection patterns, immunological, and molecular features of CGD from multiple centers in India.

Methods: A detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed.

Results: Of the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)- (44.7%) gene defect was most common, followed by (31.9%), (14.9%), and (8.5%). While variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up.

Conclusions: In India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.
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http://dx.doi.org/10.3389/fimmu.2021.625320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946827PMC
August 2021

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India.

Front Immunol 2020 8;11:619146. Epub 2021 Feb 8.

Institute of Child Health, Madras Medical College, Chennai, India.

Background: Severe Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.

Objective: To describe clinical and laboratory features of SCID diagnosed at immunology centers across India.

Methods: A detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.

Results: We obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - (36), (26), (19), (17), (15), (13), (9), (3), (3), (2), (2), (2), (2), (2), (2), (2), (1), (1), (1), (1), (1), (1), and (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).

Conclusion: We document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.
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http://dx.doi.org/10.3389/fimmu.2020.619146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897653PMC
June 2021

Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India.

Front Immunol 2020 15;11:612323. Epub 2021 Jan 15.

Department of Pediatric Hematology Oncology and Bone Marrow Transplant, Kanchi Kamakoti Childs Trust Hospital, Chennai, India.

Background: There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.

Methods: Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria.

Results: We received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 'definite XLA' and eight 'probable/possible XLA'). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. was the commonest bacterial pathogen identified followed by , and . Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14-19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients.

Conclusion: There was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge.
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http://dx.doi.org/10.3389/fimmu.2020.612323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873890PMC
June 2021

Presence of allele CYP3A4*16 does not have any bearing on carbamazepine-induced adverse drug reactions in North Indian people with epilepsy.

Indian J Pharmacol 2020 Sep-Oct;52(5):378-382

Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objectives: The objectives of this study were to determine the relationship between genetic polymorphisms in gene encodings for CYP3A4 and carbamazepine (CBZ)-induced dose-related side effects in North Indian people with epilepsy.

Patients And Methods: The current prospective study included 37 patients with CBZ-induced dose-related side effects and 102 patients who did not experience side effects while on CBZ. The genotyping for CYP3A4 allele (CYP3A4*16) was done using real-time polymerase chain reaction (RT-PCR) in Applied Biosystems 7500 RT-PCR System (USA). CBZ was administered in all patients at a dose varying from 15 to 20 mg/kg daily.

Results: Various demographic variables were comparable between the groups except that control of seizures was far better in controls. After testing, it was found that none of our patients had the presence of CYP3A4*16 allele.

Conclusion: CYP3A4*16 allele is not represented significantly in North Indian people with CBZ-induced dose-related side effects.
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http://dx.doi.org/10.4103/ijp.IJP_549_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025771PMC
December 2020

Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India.

Pediatr Allergy Immunol 2021 04 5;32(3):599-611. Epub 2020 Dec 5.

Allergy Immunology Unit, Department of Paediatrics, Advanced Paediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: There is paucity of literature on long-term follow-up of patients with hereditary angioedema (HAE) from developing countries.

Objective: This study was carried out to analyze the clinical manifestations, laboratory features, and genetic profile of 32 patients (21 male and 11 female) from 23 families diagnosed with HAE between January 1996 and December 2019.

Methods: Data were retrieved from medical records of Paediatric Immunodeficiency Clinic, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Results: Median age at onset of symptoms was 6.25 years (range 1-25 years), and median age at diagnosis was 12 years (range 2-43 years). Serum complement C4 level was decreased in all patients. All patients had low C1-esterase inhibitor (C1-INH) quantitative level (type 1 HAE). SERPING1 gene sequencing could be carried out in 20 families. Of these, 11 were identified to have a pathogenic disease-causing variant in the SERPING1 gene. While 2 of these families had a previously reported mutation, remaining 9 families had novel pathogenic variants in SERPING1 gene. Because of non-availability of C1-INH therapy in India, all patients were given long-term prophylaxis (attenuated androgens or tranexamic acid (TA) or a combination of the 2). Life-threatening episodes of laryngeal edema were managed with fresh-frozen plasma (FPP) infusions. We recorded one disease-related mortality in our cohort. This happened in spite of long-term prophylaxis with stanozolol and TA.

Conclusions: We report largest single-center cohort of patients with HAE from India. Attenuated androgens, fibrinolytic agents, and FPP may be used for management of HAE in resource-limited settings.
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http://dx.doi.org/10.1111/pai.13420DOI Listing
April 2021

Successful use of cyclosporine in epidermolysis bullosa pruriginosa.

Dermatol Ther 2020 11 10;33(6):e14489. Epub 2020 Nov 10.

Department of Immunopathology, PGIMER, Chandigarh, India.

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http://dx.doi.org/10.1111/dth.14489DOI Listing
November 2020

Metabolic Syndrome and Its Effects on Cartilage Degeneration vs Regeneration: A Pilot Study Using Osteoarthritis Biomarkers.

Indian J Orthop 2020 Sep 24;54(Suppl 1):20-24. Epub 2020 Jul 24.

Department of Orthopaedics, PGIMER, Chandigarh, India.

Background: Osteoarthritis (OA) of the knee is one of the leading causes of disability characterized by degeneration of hyaline cartilage combined with reparative processes. Its strong association with metabolic syndrome is postulated to be due to both mechanical and biochemical factors. Our study aims to study differential effect of metabolic risk factors on cartilage degeneration and regeneration at biomarker level.

Design: After screening 281 patients presenting with knee pain, 41 patients who met the selection criteria were included and were divided into metabolic (MetS) OA and non-metabolic (Non-MetS) OA phenotypes using National Cholesterol Education Programme-Adult Treatment Panel-III (NCEP-ATP-III) criteria for metabolic syndrome. Serum Cartilage Oligomeric Matrix Protein (COMP) and Procollagen type IIA N terminal Propeptide (PIIANP) levels were used as tools to assess cartilage degeneration and regeneration, respectively.

Results: 22 among 41 patients (53.66%) had metabolic syndrome. Covariates like age, gender, Kellgren Lawrence (KL) grades were comparable in both groups. MetS-OA group showed significant increase in serum COMP levels ( = 0.03) with no significant effect on serum PIIANP levels ( = 0.46). Hypertriglyceridemia showed independent association with both cartilage anabolism ( = 0.03) and catabolism ( = 0.03).

Conclusion: Metabolic syndrome, though has no effect on cartilage regeneration tends to shift cartilage homeostasis towards degeneration with hypertriglyceridemia showing significant independent effect on cartilage metabolism.
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http://dx.doi.org/10.1007/s43465-020-00145-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474006PMC
September 2020

Which Are the Optimal Criteria for the Diagnosis of Allergic Bronchopulmonary Aspergillosis? A Latent Class Analysis.

J Allergy Clin Immunol Pract 2021 01 3;9(1):328-335.e1. Epub 2020 Sep 3.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Electronic address:

Background: The ideal criteria for diagnosing allergic bronchopulmonary aspergillosis (ABPA) remain unknown because of the lack of a criterion standard. Latent class analysis using a probabilistic modeling technique can circumvent the need for a reference standard.

Objective: To compare the diagnostic performance of various criteria used for evaluating ABPA.

Methods: We prospectively enrolled consecutive cases of bronchial asthma and performed a series of investigations used for the diagnosis of ABPA. We used latent class analysis to analyze the performance of various existing and novel diagnostic criteria.

Results: Of the 543 subjects (mean age, 37 years; 319 women), 338 (62.2%) and 205 (37.8%) were labeled as "mild-to-moderate" and "severe" asthma cases, respectively. The subjects with severe asthma had a longer duration of asthma and a higher number of exacerbations in the previous year. The prevalence of Aspergillus fumigatus sensitization was 41% and 30%, using the A fumigatus-specific IgE and skin test, respectively. The prevalence of ABPA was 16%, using both the Rosenberg-Patterson and the International Society for Human and Animal Mycology (ISHAM)-ABPA Working Group criteria. The ISHAM criteria were slightly more sensitive (89% vs 81%) and specific (99% vs 98%) than the Patterson criteria. We obtained optimal diagnostic performance by altering the existing ISHAM criteria (serum total IgE >500 international units/mL, excluding the skin test, and using computed tomography of thorax instead of chest radiograph).

Conclusions: The ISHAM-ABPA Working Group criteria were only marginally better than the Patterson criteria in diagnosing ABPA among patients with asthma younger than 66 years. The diagnostic performance however improved by modifying the prevailing ISHAM criteria, but with increased cost.
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http://dx.doi.org/10.1016/j.jaip.2020.08.043DOI Listing
January 2021

Metabolic syndrome and female gender, but not methotrexate, are the important associations of significant liver fibrosis in patients with moderate-to-severe psoriasis as detected by transient elastography.

Indian J Dermatol Venereol Leprol 2020 Nov-Dec;86(6):649-655

Department of Immunopathology, PGIMER, Chandigarh, India.

Background: Many international guidelines on psoriasis management have emphasized upon the need to identify risk factors for liver fibrosis and that the risk may be increased after a certain total cumulative dose of methotrexate.

Methods: Consecutive patients with moderate-to-severe psoriasis were assessed for liver fibrosis using transient elastography and noninvasive scores. Based on the presence of significant liver fibrosis, the Odds ratio associated with various factors was calculated using logistic regression analysis. Receiver operating characteristic curves were calculated to find maximal cutoff values of noninvasive tests to detect fibrosis.

Results: In this cross-sectional study, 134 patients completed the study. Significant fibrosis (liver stiffness measurement ≥7, corresponding to F2 fibrosis or higher) was seen in 33 (24.6%) patients. Neither methotrexate exposure nor total cumulative dose of ≥1.5 was associated with significant fibrosis. Female sex (P = 0.024) and the presence of metabolic syndrome (P = 0.034) were the two variables associated with significant liver fibrosis. On logistic regression analysis, the odds ratio for the female gender and metabolic syndrome was estimated to be 2.51 (95% confidence interval - 1.09-5.81) and 2.33 (95% confidence interval - 1.03-5.27), respectively. Aspartate transaminase to platelet ratio index, nonalcoholic fatty liver disease score and the fibrosis-4 index had low sensitivity in comparison to transient elastography.

Limitations: These included small sample size, small number of patients with a total cumulative methotrexate dose of >3-4.5 g, and lack of control group consisting of healthy persons. Another is the absence of liver biopsies considered as the gold standard in the diagnosis of liver fibrosis.

Conclusions: Metabolic syndrome and female sex are associated with the development of significant liver fibrosis in patients with psoriasis. Methotrexate exposure does not seem to be significantly associated with significant liver fibrosis.
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http://dx.doi.org/10.4103/ijdvl.IJDVL_152_19DOI Listing
September 2021

The effect of methotrexate on neutrophil reactive oxygen species and CD177 expression in rheumatoid arthritis.

Clin Exp Rheumatol 2021 May-Jun;39(3):479-486. Epub 2020 Jun 23.

Rheumatology Unit, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objectives: Neutrophils are found in abundance in the synovial fluid of patients with rheumatoid arthritis (RA), where they are activated and show high reactive oxygen species (ROS) production. However, there is limited data on circulating neutrophils in peripheral blood of patients with RA in terms of ROS production, expression of activation markers and the effect of treatment with methotrexate (MTX) on ROS.

Methods: This single-centre prospective study recruited patients of RA classified as per the 2010 ACR/EULAR criteria. In the cross-sectional arm, we included three groups, treatment-naïve RA (naïve-RA), MTX-treated RA (MTX-RA) and healthy controls, and compared ROS production and surface markers of neutrophil activation. In the longitudinal arm, we studied the change in neutrophil ROS production after 8 weeks of MTX treatment in naïve-RA patients. Neutrophil ROS production was measured by flow cytometry using dihydrorhodamine-123 (DHR) and by chemiluminescence using luminol. Surface expression of CD177, CD11b and CD64 was measured by flow cytometry.

Results: This study included 103 patients (50 naïve-RA, 53 MTX-RA) and 20 controls. Both naïve-RA and MTX-RA patients showed higher ROS production than healthy controls in unstimulated neutrophils in the DHR assay (p<0.001 and p=0.004). MTX-RA patients showed significantly lower ROS production than naive-RA, in both unstimulated (p=0.004) and PMA-stimulated neutrophils in the DHR assay (p=0.03). On longitudinal follow-up of 24 naïve-RA patients, there was a significant reduction of neutrophil ROS production (by 55% from baseline) (p<0.001) after 8 weeks of MTX. Neutrophil CD177 expression was higher in both naïve-RA and MTX-RA (trend) than controls (p=0.001 and p=0.09). MTX-RA neutrophils showed lower expression of CD177 than naïve-RA (p=0.01). CD11b expression was higher in MTX-RA compared to controls (p=0.01).

Conclusions: Circulating neutrophils in RA showed higher ROS production and higher expression of CD177 and CD11b compared to controls. MTX treatment was associated with a reduction in ROS production and CD177 expression, which may be one of the mechanisms by which MTX works in RA.
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May 2021

Mystery of a Family with Recurrent Male Infant Deaths- Solved by Autopsy and Molecular Tests.

Indian J Pediatr 2021 03 26;88(3):257-262. Epub 2020 May 26.

Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

The authors report a case of a six weeks old boy who presented with acute febrile illness and progressive abdominal distension. There was a significant family history of early male sibling deaths. Autopsy showed multiorgan abscesses. Molecular test revealed final diagnosis of the child.
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http://dx.doi.org/10.1007/s12098-020-03304-0DOI Listing
March 2021

Distinct HLA and non-HLA associations in different subtypes of ANCA-associated vasculitides in North India.

Int J Rheum Dis 2020 Jul 16;23(7):958-965. Epub 2020 Apr 16.

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Aim: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease characterized by necrotizing small vessel vasculitis that can affect various organs and present multiple symptoms. Susceptibility to AAV is multifactorial and most likely caused by an amalgamation of genetic and environmental factors. The aim of the present study was to explore the distribution of human leukocyte antigen (HLA)-DRB1/DQB1, protein tyrosine phosphatase non-receptor type 22 (PTPN22) and cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian AAV patients and their associations with clinical and pathological characteristics associated with the disease.

Methods: A total of 150 AAV patients and 150 healthy controls were recruited. The clinical classification showed 128 as granulomatosis with polyangiitis (GPA) and 21 as microscopic polyangiitis. Only 1 case of eosinophilic granulomatosis with polyangiitis was encountered, which was excluded from analysis. HLA-DRB1/DQB1 alleles were determined by polymerase chain reaction-sequence-specific primer (PCR-SSP) method and single nucleotide variant genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays.

Results: A significant predispositional association of DRB1*03 and DQB1*02 alleles, were confirmed in proteinase 3 (PR3)-AAV patients, whereas DRB1*10, DRB1*14 and DQB1*05 were protective alleles in AAV, PR3-AAV and GPA patients. GG genotype of CTLA-4 + 49A/G was increased in patients as compared to controls and showed an association with AAV, PR3-AAV and GPA patients.

Conclusion: The study indicated strong genetic associations were linked with PR3 antineutrophil cytoplasmic antibody specificity and it appears that PR3-AAV and MPO-AAV have distinct genetic backgrounds.
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http://dx.doi.org/10.1111/1756-185X.13837DOI Listing
July 2020

Expression of CD40 Ligand on T Cells and Soluble CD40 Ligand in Children With Kawasaki Disease: A Single-Center Preliminary Study From North India.

J Clin Rheumatol 2021 Aug;27(5):194-200

From the Allergy Immunology Unit, Advanced Pediatrics Centre.

Background/objective: This study was done to examine the role of CD40 ligand (CD40L) in children with Kawasaki disease (KD). There is paucity of literature on this aspect of KD.

Methods: This was a case-control study of patients with KD diagnosed at the Allergy Immunology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India. CD40L expression on activated CD3+ T cells was measured using flow cytometry, and soluble CD40L (sCD40L) was measured using enzyme-linked immunosorbent assay.

Results: We included 14 children with KD, 14 healthy controls, and 12 febrile controls for the purpose of this study. Mean percentage CD40L expression was higher in patients with KD (before administration of intravenous immunoglobulin [IVIg]) as compared with normal and febrile controls. This difference was statistically significant when compared with normal control (p = 0.00; confidence interval [CI], 8.92-20.30), but was not statistically significant when compared with febrile controls (p = 0.138; CI, -3.50 to 22.08). CD40L expression decreased after giving IVIg, but the difference was not statistically significant (p = 0.073; CI, -1.04 to 19.73). Mean sCD40L values increased significantly after giving IVIg (when repeated after a median period of 11 days; p = 0.001; CI, -0.77 to -0.29). There was no statistically significant difference between mean sCD40L in patients with KD (before giving IVIg) as compared with normal and febrile controls (p = 0.42; CI, -1.11 to -0.51 and p = 0.641; CI, -0.37 to 0.57, respectively).

Conclusions: CD40L may have important role in the pathogenesis of KD. However, these results need to be validated in larger multicenter studies.
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http://dx.doi.org/10.1097/RHU.0000000000001283DOI Listing
August 2021

Efficacy of cross-match compatible platelets in multi transfused haemato-oncology patients refractory to platelet transfusion.

Transfus Apher Sci 2019 Dec 22;58(6):102657. Epub 2019 Oct 22.

Department of Transfusion Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Platelet refractoriness, which leads to platelet transfusion failure resulting in significant morbidity and long hospital stay, is routinely not investigated.

Aims: To determine the efficacy of cross-match compatible platelets in multi-transfused alloimmunized hemato-oncological patients refractory to platelet transfusion.

Materials And Method: 149 ABO compatible single donor apheresis platelet transfusions given to 38 alloimmunized refractory patients. Corrected Count Increment (CCI) <5000 (1 h) was taken to define refractoriness. Solid-phase red cell adherence assay was used to determine the alloimmunization status and platelet cross-matching. Post Transfusion Platelet Increment, CCI and the Percentage Platelet Recovery were used to monitor the effectiveness of platelet transfusion. ANOVA test followed by Post hoc test Tukey HSD used to compare group means and classified into three groups depending upon the cross-matching and compatibility status. Categorical data was analysed for various outcomes using Pearson's chi square test or Fischer exact test.

Result: Patients showed statistically significant recovery in terms of PPI, CCI and PPR at 1 h post SDAP transfusions when they received cross-matched compatible platelets. The one-hour CCI was significantly higher for cross-match-compatible platelets (19173 ± 2692) than for incompatible (5888 ± 1526) and for uncross-matched (8140 ± 1480). Forty four (97.8%) of 45 cross-matched compatible platelet transfusion episodes showed a satisfactory response in terms of PPI and CCI values as compared to 50 % and 53.9% in uncross-matched group respectively (p < 0.0001).

Conclusion: Platelet cross-matching is an effective intervention in the management of multi-transfused alloimmunized Haemato-oncological patients, refractory to platelet transfusion.
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http://dx.doi.org/10.1016/j.transci.2019.09.010DOI Listing
December 2019

Role of anti-tissue transglutaminase IgA+IgG antibodies in detection of potential celiac disease in patients with type 1 diabetes.

Indian J Med Res 2019 Jan;149(1):18-25

Department of Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Background & Objectives: : Celiac disease (CD) can exist in various forms in type 1 diabetes (T1D) patients and can remain undetected, leading to severe complications. This study was aimed to evaluate five commercially available anti-tissue transglutaminase (tTG) ELISA kits with distinct formats for the detection of CD and potential CD in T1D patients. Clinical and demographic profiles of the patients with different disease subsets were also studied.

Methods: : Fifty T1D patients with classical and non-classical symptoms of CD and 100 T1D patients without any symptoms of CD were included in this study. Anti-tTG autoantibody levels were estimated by five ELISA kits followed by histological examination of duodenal biopsy. HLA DQ2-DQ8 and DRB1-DQB1 typing was done, and serum levels for transforming growth factor (TGF)-β1 were also estimated.

Results: : Assay format detecting anti-tTG IgA antibodies against recombinant antigens along with neopeptides of gliadin was most efficient in the detection of CD in symptomatic patients, and assay format detecting IgA+IgG helped in the detection of potential CD in asymptomatic T1D patients. These findings were supported by histological examination and human leucocyte antigen analysis. Patients with potential CD were found to have markedly deranged glycaemic control parameters and also had significantly raised serum levels of TGF-β1, (P <0.05) compared to T1D patients.

Interpretation & Conclusions: : Potential CD can be frequently seen in T1D patients. This can be attributed to the dietary patterns prevalent in the subcontinent and the genetic basis of the disease. Anti-tTG IgA+IgG antibodies can be useful in the detection of these potential CD cases in T1D patients. Early intervention with gluten-free diet can be considered in these patients for better disease management.
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http://dx.doi.org/10.4103/ijmr.IJMR_1136_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507530PMC
January 2019

Reduced Natural Killer Cell Subsets in Perinatally Acquired Long-Term Non-Progressor Human Immunodeficiency Virus-Infected Children.

AIDS Res Hum Retroviruses 2019 05 27;35(5):437-443. Epub 2019 Feb 27.

1 Department of Pediatrics, Advance Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Lymphocyte subsets of long-term non-progressor (LPNT) HIV-infected children is a less studied aspect of HIV infection. Evaluation of different lymphocyte subsets was done in HIV-infected children ≥8 years of age. Subjects were divided in two groups-group 1 (LTNP), treatment-naive with CD4 ≥ 500 cells/μL ( = 20); group 2, non-long-term non-progressor (nLTNPs) receiving antiretroviral therapy (ART) with CD4 count ≤500 on at least one occasion ( = 21). Group 3 comprised age-, sex-matched healthy controls (HCs,  = 20). Lymphocyte subsets were acquired with a flow cytometer (Navios; Beckman Coulter), and data were analyzed using Kaluza flow analysis software. The mean ages were 12.1 (±2.4 SD) and 12.5 (±2.7) years with mean duration of follow-up of 6.8 (±3.4) and 5.6 (±1.95) years in LTNP and nLTNP subjects, respectively. The mean duration of ART was 5.17 years for group 2. Absolute count and percentage of CD4 T cells was lower in nLTNPs than in LTNPs. Cytotoxic T cells were high in both HIV-infected groups compared with HCs. Natural killer (NK) cells were found to be significantly lower in LTNP and nLTNP groups compared with HCs ( ≤ .000003 and  ≤ .00003, respectively). Naïve B cells were more in HIV-infected individuals than in HCs. NK cells were significantly lower in LTNP and nLTNP groups. Immune reconstitution was comparable in children initiated with ART early versus long-term HIV-infected children receiving no ART.
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http://dx.doi.org/10.1089/AID.2018.0243DOI Listing
May 2019

Monoclonal Gammopathy of Unclear Significance in a Child with Wiskott-Aldrich Syndrome: a Rare Occurrence.

J Clin Immunol 2019 01 3;39(1):7-10. Epub 2019 Jan 3.

Allergy and Immunology Unit, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s10875-018-0585-9DOI Listing
January 2019

Clinical and molecular features of X-linked hyper IgM syndrome - An experience from North India.

Clin Immunol 2018 10 25;195:59-66. Epub 2018 Jul 25.

Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG). We analyzed the clinical and laboratory features of ten patients with XLHIGM, who were diagnosed at a tertiary care hospital in North India. Most common infections were sinopulmonary infections (80%) and diarrhea (50%). Sclerosing cholangitis and necrotising fasciitis were noted in one patient each. Three novel mutations in CD40LG (c.429_429 delA, p. G144DfsX5; c.500 G > A, p.G167E and c.156 G > C, p.K52 N) were detected. In addition, we found one missense mutation, two splice site mutations and two large deletions, which have been previously reported. Four (4) patients had expired at the time of analysis. We report the first series of XLHIGM from North India where we have documented unique features such as pulmonary alveolar proteinosis and infections with Mycobacterium sp.
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http://dx.doi.org/10.1016/j.clim.2018.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666391PMC
October 2018

A randomised trial of voriconazole and prednisolone monotherapy in acute-stage allergic bronchopulmonary aspergillosis complicating asthma.

Eur Respir J 2018 09 18;52(3). Epub 2018 Sep 18.

Dept of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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http://dx.doi.org/10.1183/13993003.01159-2018DOI Listing
September 2018

STAT3-Mediated Transcriptional Regulation of Osteopontin in STAT3 Loss-of-Function Related Hyper IgE Syndrome.

Front Immunol 2018 17;9:1080. Epub 2018 May 17.

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Hyper-IgE syndrome (HIES) caused by loss-of-function (LOF) mutations in STAT3 gene (STAT3 LOF HIES) is associated with dental and facial abnormalities in addition to immunological defects. The role of STAT3 in the pathogenesis of the dental/facial features is, however, poorly elucidated.

Objectives: Since mechanism of cellular resorption of mineralized tissues such as bone and teeth are similar, we attempted to study the expression of genes involved in bone homeostasis in STAT3 LOF HIES.

Methods: Peripheral blood mononuclear cells from healthy controls (HCs), STAT3 LOF HIES patients, STAT3 PC-3 cells and STAT3 LNCaP cells were stimulated with IL-6 and quantitative PCR array was performed to study the relative mRNA expression of 43 pre-selected genes. PCR array finding were further evaluated after induced STAT3 inhibition.

Results: Osteopontin (OPN) gene was seen to be significantly upregulated after IL-6 stimulation in HC (mean fold change 18.6,  = 0.01) compared with HIES subjects. Inhibition of STAT3 signaling by followed by IL-6 stimulation abrogated the OPN response in HCs suggesting that IL-6-induced STAT3 signaling regulates expression. Bioinformatics analysis predicted the presence of STAT3 response element TTCCAAGAA at position -2005 of the OPN gene.

Conclusion: Regulation of OPN gene through IL-6-mediated STAT3 activation and its significant dysregulation in STAT3 LOF HIES subjects could make OPN a plausible candidate involved in the pathogenesis of dental/facial manifestations in HIES.
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http://dx.doi.org/10.3389/fimmu.2018.01080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966547PMC
July 2019

Role of Direct Immunofluorescence in Cutaneous Small-Vessel Vasculitis: Experience From a Tertiary Center.

Am J Dermatopathol 2018 Sep;40(9):661-666

Departments of Histopathology.

Skin is commonly affected by vasculitic process and often subjected to biopsy. Cutaneous vasculitis can be either primary or part of a systemic vasculitic process. This study was conducted to evaluate the diagnostic utility of direct immunofluorescence (DIF) in determination of etiology of cutaneous vasculitis. All histologically proven cases of cutaneous vasculitis over the past two and half years were retrospectively analyzed along with their clinical and DIF findings (IgG, IgA, IgM, and C3). Within this study period, a total of 198 cases of small-vessel vasculitis were diagnosed based on skin biopsy and DIF findings. The mean age of patients was 31.2 years (range 1-84 years) with slight male dominance (M:F ratio 1.06:1). Henoch-Schonlein purpura/IgA vasculitis was the commonest clinical diagnosis (31%), followed by urticarial vasculitis (11%) and others. Idiopathic vasculitis was suspected in 33% cases. Overall, DIF was positive in 60% (119/198) cases, with vascular deposition of IgA being commonest, followed by C3. The clinical diagnosis of Henoch-Schonlein purpura could be confirmed in 61.5% (40/65) cases by DIF, whereas another 20 unsuspected cases were picked up as IgA vasculitis based on DIF findings. DIF findings confirmed lupus vasculitis in 50% cases. Other cases showed variable nonspecific deposition of C3 and IgM in 42% cases. DIF can be highly useful to classify cutaneous vasculitis, with maximum efficacy for diagnosis of IgA vasculitis and lupus vasculitis. It can aid in the accurate diagnosis even when the histological changes are minimal. All cases of suspected cutaneous vasculitis should be subjected to DIF.
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http://dx.doi.org/10.1097/DAD.0000000000001170DOI Listing
September 2018

A mechanistic approach to explore the neuroprotective potential of zonisamide in seizures.

Inflammopharmacology 2018 Aug 11;26(4):1125-1131. Epub 2018 Apr 11.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Background: Epilepsy, a disease of the brain, is one of the most common serious neurological conditions. It is associated with a group of processes which alter energy metabolism, interrupt cellular ionic homeostasis, cause receptor dysfunction, activate inflammatory cascade, alter neurotransmitter uptake and result in neuronal damage. The increasing knowledge and understanding about the basis of neuronal changes in epilepsy lead to investigate the mechanistic pathway of neuroprotective agents in epilepsy. With this background, the present study is designed to reveal the molecular and biochemical mechanisms involved in the neuroprotective potential of zonisamide in epilepsy.

Methods: Seizure-induced neuronal damage was produced by maximal electroshock seizures in animals. The oxidative stress and neuroinflammatory and apoptotic markers were assessed in the brain tissue of animals.

Results And Discussion: The present findings revealed that zonisamide treatment prevented the development of seizures in animals. Seizures-induced free radicals production and neuroinflammation were markedly ameliorated by zonisamide administration. In conclusion, the present study demonstrated the mechanisms behind the strong neuroprotective potential of zonisamide against seizures by attenuating the oxidative stress, inflammatory cascade and neuronal death associated with progression of seizures. It can be further developed as a neuroprotective agent for epilepsy and other neurodegenerative disorders.
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http://dx.doi.org/10.1007/s10787-018-0478-9DOI Listing
August 2018

The effect of intra-articular allogenic platelet rich plasma in Dunkin-Hartley guinea pig model of knee osteoarthritis.

Muscles Ligaments Tendons J 2017 Jul-Sep;7(3):426-434. Epub 2018 Jan 10.

Postgraduate Institute of medical education and research, Chandigarh, India.

Objectives: To investigate the pathway for disease modifying effect of the PRP in osteoarthritis of knee.

Design: Two experimental models (group I and II) of Twelve Dunkin-Hartley guinea pigs each were enrolled as a part of a prospective controlled experimental study. One knee was enrolled for intervention and the other knee of the same animal used as control, the intervention being three intra-articular allogenic PRP injections given at a weekly interval. Equal volume of isotonic saline injection were given simultaneously in the control knees. Six animals from each model (subgroup IA, IIA) were euthanized at three months and the remaining six (subgroup IB, IIB) at six months post intervention. Samples of synovial fluid were collected from each knee joint for COMP level analysis by ELISA and bilateral knee joints were harvested for histopathological assessment of articular cartilage and synovium at the time of euthanasia.

Results: Mean synovial fluid COMP concentration was significantly lower in PRP treated knees (p<0.05) at three months. On histological examination mean synovitis scores and synovial vascularity were significantly lower in PRP treated knees as compared to controls at both three and six months (p < 0.05). Additionally mean articular cartilage degeneration was significantly lower in PRP treated knees in group 1 only (p<0.05).

Conclusion: Our preliminary data from the study has shown some evidence of positive influence of PRP in knee OA, possibly due to its anti-inflammatory effect and disease modifying effect, shown by short-term chondro-protective effect in PRP injected knees.

Level Of Evidence: V.
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http://dx.doi.org/10.11138/mltj/2017.7.3.426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774915PMC
January 2018

A Randomized Trial of Itraconazole vs Prednisolone in Acute-Stage Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

Chest 2018 03 11;153(3):656-664. Epub 2018 Jan 11.

Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Whether itraconazole monotherapy is effective in the acute stage of allergic bronchopulmonary aspergillosis (ABPA) remains unknown. The goal of this study was to compare the efficacy and safety of itraconazole and prednisolone monotherapy in ABPA.

Methods: Treatment-naive subjects with ABPA complicating asthma (January 2012 to December 2013) were randomized to receive either oral itraconazole or prednisolone for 4 months. The study was not blinded. The primary outcomes were proportion of subjects exhibiting a composite response after 6 weeks, percent decline in IgE after treatment, and numbers of subjects experiencing exacerbation. The secondary outcomes included the time to first exacerbation, change in lung function, and treatment-related adverse effects.

Results: A total of 131 subjects (prednisolone group, n = 63; itraconazole group, n = 68) were included in the study. The number of subjects exhibiting a composite response was significantly higher in the prednisolone group compared with the itraconazole group (100% vs 88%; P = .007). The percent decline in IgE after 6 weeks and 3 months and the number of subjects with exacerbations after 1 and 2 years of treatment were similar in the two groups. The time to first exacerbation (mean: 437 vs 442 days) and the improvement in lung function after 6 weeks was also similar in the two groups. The occurrence of side effects was significantly higher in the glucocorticoid arm (P < .001).

Conclusions: Prednisolone was more effective in inducing response than itraconazole in acute-stage ABPA. However, itraconazole was also effective in a considerable number and, with fewer side effects compared with prednisolone, remains an attractive alternative in the initial treatment of ABPA.

Trial Registry: ClinicalTrials.gov; No.: NCT01321827; URL: www.clinicaltrials.gov).
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http://dx.doi.org/10.1016/j.chest.2018.01.005DOI Listing
March 2018

Infectious and non-infectious complications in primary immunodeficiency disorders: an autopsy study from North India.

J Clin Pathol 2018 May 28;71(5):425-435. Epub 2017 Sep 28.

Department of Paediatrics (Allergy and Immunology Unit), Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.

Background: Primary immunodeficiency disorders (PID) include a wide spectrum of inherited disorders characterised by functional abnormalities of one or more components of the immune system. Recent updates from the genomic data have contributed significantly to its better understanding with identification of new entities. Diagnosis is always challenging due to their variable clinical presentation. With the evolution of molecular diagnosis, many of these children are being diagnosed early and offered appropriate therapy. However, in developing countries, early diagnosis is still not being made: as a result these patients succumb to their disease. Autopsy data on PID is notably lacking in the literature with histopathological evaluation of PID being limited to rare case reports.

Objective: To analyse the clinical, immunologic (including mutational) and morphologic features at autopsy in 10 proven and suspected cases of primary immunodeficiency disorders diagnosed at our Institute over the past decade.

Methods: Study includes a detailed clinico-pathological analysis of 10 proven and suspected cases of primary immunodeficiency disorders.

Results: A varied spectrum of infectious and non-infectious complications were identified in these cases of which fungal infections were found to be more frequent compared with viral or bacterial infections. Rare and novel morphological findings, like granulomatous involvement of the heart in a patient with chronic granulomatous disease, systemic amyloidosis in a teenage girl with X-linked agammaglobulinemia, are highlighted which is distinctly lacking in the literature.

Conclusions: The present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention.
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http://dx.doi.org/10.1136/jclinpath-2017-204708DOI Listing
May 2018

Allo-specific immune response profiles indicative of acute rejection in kidney allografts using an in vitro lymphocyte culture-based model.

Clin Exp Nephrol 2018 Apr 28;22(2):465-473. Epub 2017 Aug 28.

Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Ability to predict the manner in which a recipient's immune system would respond to a transplanted graft by analyzing cytokine profiles of the "allograft antigen sensitized" recipient lymphocytes in vitro might provide a means to identify patients at risk to adverse clinical endpoints.

Methods: Cytokine/chemokine gene expression profiles of peripheral blood mononuclear cells co-cultured with allograft antigen-pulsed macrophages were studied in 49 renal transplant recipients-12 with acute cellular rejection (ACR) with or without antibody-mediated rejection (AMR), 7 with AMR (without ACR), and 30 with stable allografts (SA). An 86-gene inflammatory cytokines and receptors PCR array was used to measure fold changes in gene expression between pulsed and un-pulsed cultures.

Results: On linear discriminant analysis and multivariate analysis of variance, a gene set comprising C3, CCL3, IL1B, TOLLIP, IL10, CXCL5, ABCF1, CCR3, IL10RB, CXCL1, and IL1R1 differentiated the ACR-AMR from the SA group. Similarly, a gene set comprising IL10, C3, IL37, IL1B, CCL3, CARD18, and TOLLIP differentiated the AMR from the SA group. No significant difference was found between the ACR-AMR vs AMR groups.

Conclusion: Distinct post in vitro stimulation cytokine profiles at the time of transplantation thus correlated with the occurrence of post-transplantation rejection episodes which indicated feasibility of this in vitro model to assess the recipient's anti-graft response at an early stage.
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http://dx.doi.org/10.1007/s10157-017-1469-7DOI Listing
April 2018
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